Decision Support for Low-Risk Prostate Cancer

Introduction

Over the past decades, increasing numbers of men have been faced with the diagnosis of prostate cancer. Conversely, prostate cancer mortality rates have decreased. In addition, men are more often diagnosed at an earlier stage of the disease. The obvious reason for these profound changes is the introduction of the prostate-specific antigen (PSA) test for the early detection of prostate cancer. Early detection of prostate cancer at a more favorable stage allows the cancer to be treated with curative, rather than palliative, intend. Screening for prostate cancer using PSA was indeed shown to reduce the prostate-cancer-specific mortality rate by 21% after 13 years of follow-up in the largest randomized prostate cancer screening trial. A major disadvantage is the detection of many additional prostate cancers, with an increase in prostate cancer incidence by over 50%. Many of these additionally identified cancers are likely not to result in any symptoms or death during a man’s lifetime. In fact, it is estimated that 50% of men diagnosed through screening have these so-called “overdiagnosed” prostate cancer. The presence of many nonaggressive tumors has already been observed in autopsy studies, which showed that prostate cancer was present in a large percentage (10–30% depending on age) of men who died of other causes. Because of the introduction of the PSA test resulting in subsequent prostate biopsies, this large reservoir of prostate cancers is now detected. Hence, radical treatment of PSA-detected tumors will for most men not result in any survival benefit. It may however lead to side-effects such as impotency or incontinence, decreasing quality of life in a substantial number of men. A way of avoiding the side-effects of radical treatment is to offer these patients active surveillance. This treatment option aims to avoid or delay treatment for most, while by monitoring tumor progression be able to offer radical treatment for those who benefit. Men diagnosed today with early detected prostate cancer are thus facing the difficult choice of radical treatment with its likely low benefit, but substantial risks of side-effects, versus conservative treatment, which might risk losing the benefit obtained by early detection. In this chapter, we will discuss some of the tools that are available to help men to choose between active treatment of their prostate cancer or to opt for the more conservative approach of active surveillance.

Defining indolent prostate cancer

Indolent prostate cancer is defined as a tumor that will not result in symptoms or death during a man’s lifetime if left untreated. The dynamic aspect of this definition makes it difficult to operationalize. A tumor that might be moderately progressive over time could be no threat for a man with a short life expectancy, but might become problematic (e.g., metastasize or cause symptoms) for a man with a longer life. Furthermore, no single parameter yet will provide definitive information on future tumor development. Last, as tumor progression in a low-risk prostate cancer group is relatively rare and takes usually at least a decade to develop, statistical evaluation of this end-point is difficult. Therefore, several other definitions were proposed to indicate tumors that are latent and have low probabilities of developing symptoms, based on parameters that do not require follow-up in time. The most common definition of indolent disease is an organ-confined tumor, ≤0.5 cm ³ , with no Gleason grade 4 or 5. This definition requires the removal of the prostate for pathological evaluation. In a conservative treatment strategy low-risk tumors are therefore defined as tumors with a high probability of being indolent on radical prostatectomy. Because the tumor is not removed and progression could thus occur, reevaluation of its low-risk character through time will be necessary. A summary of the different definitions used in the context of indolent/low-risk prostate cancer is given in Table 24.1 .

Several clinical definitions were proposed to select men with high likelihood of indolent prostate cancer on radical prostatectomy. These men are best suitable for a conservative treatment approach. Most definitions use a combination of low tumor grade (Gleason ≤6), localized disease (cT1c-cT2c), low PSA or PSA density (PSA ≤10–15, PSA-density ≤0.15–0.2), and small tumor volume (≤2 cores positive on prostate biopsy, ≤50% tumor involvement per core). Different definitions used for the selection of men on active surveillance studies are shown in Table 24.2 . Although commonly used in clinical practice, these rule-based definitions have some obvious disadvantages. The most important limitation of these criteria is that much of the predictive value of individual prognostic factors is lost. For example, a man with a PSA of 2 ng/mL and a man with a PSA of 10 ng/mL would both meet the same definition if the criterion is: PSA ≤10 ng/mL. Using the definition would assume these men are similar in risk of having indolent disease, while clearly the man with the lower PSA will have a higher probability of indolent disease. Moreover, using a rule-based definition of indolent disease exerts equal value to all individual risk factors. Both a man with a Gleason score of 7 and a man with a PSA of 10.5 ng/mL would not fit the rule-based definition. The first might have a truly higher chance of having aggressive disease and therefore not be suitable for conservative management, while the second may only marginally differ in risk of being indolent and could therefore still consider a nonradical approach. Combining risk factors into an individual risk estimation (risk-based), instead of “eligible” or “noneligible” (rule-based), may better inform the patient and his physician and help to make a more conscious decision on treatment choice.